Dysfunction of central control of breathing in amyotrophic lateral sclerosis

Abstract

Dysfunction in central control of breathing in some amyotrophic lateral sclerosis (ALS) patients is not adequately detected with standard evaluation for respiratory dysfunction. Nocturnal oximetry reveals periodic desaturations despite normal respiratory muscle movements. Continuous diaphragmatic electromyography has provided in vivo data consistent with impaired central control of diaphragm motor units. Current understanding of central control of breathing identifies the pre-Botzinger complex as the inspiratory rhythm generator. Animal models of pre-Botzinger complex neurodegeneration demonstrate rapid eye movement-related central sleep apneas progressing to loss of rapid eye movement sleep, also apparent in some ALS patients. Evidence supports the hypothesis that dysfunction in central control of breathing in some ALS patients may be related to pre-Botzinger complex degeneration. As the impact dysfunction of central control of breathing has on ALS becomes better defined the current standard of evaluating respiratory dysfunction in ALS patients may need updating. Muscle Nerve 56: 197-201, 2017.

Breathing: Motor Control of Diaphragm Muscle

“…In ALS, degeneration and abnormal activity of the cortical motor control centers occurs in patients (60,76,214) and rodent models (49,51,136,160). There is growing evidence that similar dysfunctions of the central control of breathing may pose additional difficulties in generating adequate ventilator and expulsive behaviors of the respiratory pump (86). Nocturnal hypoventilation and sleepdisordered breathing is common in ALS (5,6,24,86), with nocturnal hypoxia observed in patients with preserved diaphragm and phrenic nerve functions (5,6,24).…”

“…There is growing evidence that similar dysfunctions of the central control of breathing may pose additional difficulties in generating adequate ventilator and expulsive behaviors of the respiratory pump (86). Nocturnal hypoventilation and sleepdisordered breathing is common in ALS (5,6,24,86), with nocturnal hypoxia observed in patients with preserved diaphragm and phrenic nerve functions (5,6,24). The neuronal populations that govern diaphragm muscle pump activity may degenerate together or be asymmetrically affected.…”

Unstable control of breathing can lead to ineffective noninvasive ventilation in amyotrophic lateral sclerosis

“…Respiratory problems in ALS patients are derived from respiratory muscle weakness due to motor neuron degeneration. However, based on the results of recent studies, some authors suggest the involvement of voluntary and involuntary components of central control of breathing in ALS [24, 25]. Nocturnal desaturations have been reported in both NREM and REM sleep stages in ALS patients with preserved respiratory function and intact electrodiagnostic tests [26, 27].…”

“…[30] found that, in some ALS patients with minimal or absent electromyographic spontaneous activity of the diaphragm, direct stimulation produces a brisk contraction, suggesting the preservation of the corticorespiratory pathways and the probable degeneration of the central respiratory centres. The proposed areas involved include the medullary dorsal and ventral respiratory pre-motor neurons and the interneurons of the pre-Bötzinger complex [24, 25].…”

Central sleep apnoea: not just one phenotype

“…By increasing ventilatory drive, ticagrelor induced CSA both in naïve patients and continuous positive airway pressure (CPAP)-treated OSA patients [52,53]. • Related to central nervous system depression or respiratory muscle peripheral weakness: Several neurological conditions, such as multiple-system atrophy [54], amyotrophic lateral sclerosis [55], multiple sclerosis [56] and neuromuscular disease [57], are associated with CSA, resulting from impaired central command and/or peripheral muscle weakness. There is insufficient prevalence data for CSA in these populations to form robust conclusions [17,58].…”